Randomized Trial of Pleural Fluid Drainage Frequency in Patients with Malignant Pleural Effusions. The ASAP Trial.

RATIONALE: Patients with malignant pleural effusions have significant dyspnea and shortened life expectancy. Indwelling pleural catheters allow patients to drain pleural fluid at home and can lead to autopleurodesis. The optimal drainage frequency to achieve autopleurodesis and freedom from catheter has not been determined. OBJECTIVES: To determine whether an aggressive daily drainage strategy is superior to the current standard every other day drainage of pleural fluid in achieving autopleurodesis. METHODS: Patients were randomized to either an aggressive drainage (daily drainage; n = 73) or standard drainage (every other day drainage; n = 76) of pleural fluid via a tunneled pleural catheter. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the incidence of autopleurodesis following the placement of the indwelling pleural catheters. The rate of autopleurodesis, defined as complete or partial response based on symptomatic and radiographic changes, was greater in the aggressive drainage arm than the standard drainage arm (47% vs. 24%, respectively; P = 0.003). Median time to autopleurodesis was shorter in the aggressive arm (54 d; 95% confidence interval, 34-83) as compared with the standard arm (90 d; 95% confidence interval, 70 to nonestimable). Rate of adverse events, quality of life, and patient satisfaction were not significantly different between the two arms. CONCLUSIONS: Among patients with malignant pleural effusion, daily drainage of pleural fluid via an indwelling pleural catheter led to a higher rate of autopleurodesis and faster time to liberty from catheter. Clinical trial registered with www.clinicaltrials.gov (NCT 00978939).

Efficacy and safety of high-dose chemotherapy with autologous stem cell transplantation in senior versus younger adults with newly diagnosed multiple myeloma.

We retrospectively studied 340 fit patients with multiple myeloma (MM) who underwent autologous stem cell transplantation (ASCT). We hypothesized that progression-free survival (PFS) of older patients was non-inferior to that of younger patients after ASCT. Our null hypothesis was that the PFS hazard ratio (HR) for a 5-year increase in age was ≥1.05; the alternative (non-inferiority) hypothesis was that the HR was ≤1. The observed HR was 0.94 (95% confidence interval [CI] 0.86-1.03); since the CI upper bound was <1.05, we reject the null hypothesis and conclude that PFS in older patients was at least as good as in younger patients. We cannot reject an analogous null hypothesis for overall survival (HR 1.06 [95% CI 0.94-1.19]), since the CI upper bound >1.05. Toxicity was similar across ages and transplant-related mortality was minimal. 28% of subjects <65 versus 45% of those ≥65 received maintenance therapy. In summary, ASCT prolongs PFS equally well in older vs. younger adults. Although we cannot exclude maintenance as a confounder, these data support ASCT for fit seniors with MM.

Preoperative or postoperative radiotherapy versus surgery alone for retroperitoneal sarcoma: a case-control, propensity score-matched analysis of a nationwide clinical oncology database.

BACKGROUND: Recruitment into clinical trials for retroperitoneal sarcoma has been challenging, resulting in termination of the only randomised multicentre trial in the USA investigating perioperative radiotherapy. Nonetheless, use of radiotherapy for retroperitoneal sarcoma has increased over the past decade, substantiated primarily by its established role in extremity sarcoma. In this study, we used a nationwide clinical oncology database to separately compare overall survival for patients with retroperitoneal sarcoma who had surgery and preoperative radiotherapy or surgery and postoperative radiotherapy versus surgery alone. METHODS: We did two case-control, propensity score-matched analyses of the National Cancer Data Base, which included adult patients with retroperitoneal sarcoma who were diagnosed from 2003 to 2011. Patients were included if they had localised, primary retroperitoneal sarcoma. Patients were classified into three groups based on use of radiotherapy: preoperative radiotherapy, postoperative radiotherapy, and no radiotherapy (surgery alone). Patients were excluded if they received both preoperative radiotherapy and postoperative radiotherapy, or if they received intraoperative radiotherapy. Parallel propensity score-matched datasets were created for patients who received preoperative radiotherapy versus those who received no radiotherapy and for patients who received postoperative therapy versus those who received no radiotherapy. Propensity scores were calculated with logistic regression, with multiple imputation and backwards elimination, with a significance level to stay of 0·05. Matching was done with a nearest-neighbour algorithm and matched 1:2 for the preoperative radiotherapy dataset and 1:1 for the postoperative radiotherapy dataset. The primary objective of interest was overall survival for patients who received preoperative radiotherapy or postoperative radiotherapy compared with those who received no radiotherapy within the propensity score-matched datasets. FINDINGS: 9068 patients were included in this analysis: 563 in the preoperative radiotherapy group, 2215 in the postoperative radiotherapy group, and 6290 in the no radiotherapy group. Matching resulted in two comparison groups (preoperative radiotherapy vs no radiotherapy, and postoperative radiotherapy vs no radiotherapy) with negligible differences in all demographic, clinicopathological, and treatment-level variables. In the matched case-control analysis for preoperative radiotherapy median follow-up time was 42 months (IQR 27-70) for the preoperative radiotherapy group versus 43 months (25-64) for the no radiotherapy group; median overall survival was 110 months (95% CI 75-not estimable) versus 66 months (61-76), respectively. In the matched case-control analysis for postoperative radiotherapy median follow-up time was 54 months (IQR 32-79) for patients in the postoperative radiotherapy group and 47 months (26-72) for patients in the no radiotherapy group; median overall survival was 89 months (95% CI 79-100) versus 64 months (59-69), respectively. Both preoperative radiotherapy (HR 0·70, 95% CI 0·59-0·82; p<0·0001) and postoperative radiotherapy (HR 0·78, 0·71-0·85; p<0·0001) were significantly associated with improved overall survival compared with surgery alone. INTERPRETATION: To the best of our knowledge, this is the largest study to date of the effect of radiotherapy on overall survival in patients with retroperitoneal sarcoma. Radiotherapy was associated with improved overall survival compared with surgery alone when delivered as either preoperative radiotherapy or postoperative radiotherapy. Together with the results from the ongoing randomised EORTC trial (62092-22092; NCT01344018) investigating preoperative radiotherapy for retroperitoneal sarcoma pending, these data might provide additional support for the increasing use of radiotherapy for patients with retroperitoneal sarcoma undergoing surgical resection. FUNDING: Department of Surgery, Duke University School of Medicine.

Efficacy of a Nurse-Delivered Intervention to Prevent and Delay Postpartum Return to Smoking: The Quit for Two Trial.

INTRODUCTION: Most pregnant women who quit smoking return to smoking postpartum. Trials to prevent this return have been unsuccessful. We tested the efficacy of a nurse-delivered intervention in maintaining smoking abstinence after delivery among pregnant women who quit smoking that was tailored on their high risk of relapse (eg, had strong intentions to return). METHODS: We recruited 382 English-speaking spontaneous pregnant quitters from 14 prenatal clinics and randomized them to receive either a smoking abstinence booklet plus newsletters about parenting and stress (control) or a nurse-delivered smoking abstinence intervention that differed in intensity for the high and low risk groups. Our primary outcome was smoking abstinence at 12 months postpartum. RESULTS: Using intent-to-treat analyses, there was a high rate of biochemically validated smoking abstinence at 12 months postpartum but no arm differences ( CONTROL: 36% [95% confidence interval [CI]: 29-43] vs. INTERVENTION: 35% [95% CI: 28-43], P = .81). Among women at low risk of returning to smoking, the crude abstinence rate was significantly higher in the control arm (46%) than in the intervention arm (33%); among women at high risk of returning to smoking, the crude abstinence rate was slightly lower but not different in the control arm (31%) than in the intervention arm (37%). CONCLUSIONS: Low-risk women fared better with a minimal intervention that focused on parenting skills and stress than when they received an intensive smoking abstinence intervention. The opposite was true for women who were at high risk of returning to smoking. Clinicians might need to tailor their approach based on whether women are at high or low risk of returning to smoking. IMPLICATIONS: Results suggest that high-risk and low-risk women might benefit from different types of smoking relapse interventions. Those who are lower risk of returning to smoking might benefit from stress reduction that is devoid of smoking content, whereas those who are higher risk might benefit from smoking relapse prevention.

Baseline Prostate Atrophy is Associated with Reduced Risk of Prostate Cancer in Men Undergoing Repeat Prostate Biopsy.

PURPOSE: We evaluated whether the presence and severity of baseline prostate atrophy in men with initial biopsy negative for prostate cancer was associated the risk of subsequent prostate cancer detection in a clinical trial with scheduled study mandated biopsies. MATERIALS AND METHODS: We retrospectively analyzed the records of 3,084 men 50 to 75 years old with prostate specific antigen between 2.5 and 10 ng/ml, and a prior negative biopsy in the placebo arm of the REDUCE (Reduction by Dutasteride of Prostate Cancer Events) study who completed at least 1 per-protocol biopsy. Prostate cancer (defined as present or absent) and prostate atrophy (graded as absent, mild or moderate/marked) was assessed by central pathology review. The association of baseline atrophy with positive 2 and 4-year repeat biopsies was evaluated with logistic regression, controlling for baseline covariates. RESULTS: Baseline prostate atrophy was detected in 2,143 men (70%) and graded as mild and moderate/marked in 1,843 (60%) and 300 (10%) baseline biopsies, respectively. Patients with atrophy were older and had a larger prostate, and more acute and chronic prostate inflammation. At 2-year biopsy the prostate cancer incidence was 17% (508 cases). Baseline atrophy was significantly associated with lower prostate cancer risk (univariable and multivariable OR 0.60, 95% CI 0.50-0.74 and OR 0.67, 95% CI 0.54-0.83, p <0.001, respectively) at the 2-year biopsy. These results were similar at the 4-year biopsy (univariable and multivariable OR 0.70, 95% CI 0.53-0.93 and OR 0.72, 95% CI 0.53-0.97, p = 0.03, respectively). Relative to no atrophy the prostate cancer risk at the 2-year repeat biopsy was lower for mild atrophy (OR 0.69, 95% CI 0.55-0.86) and moderate/marked atrophy (OR 0.51, 95% CI 0.34-0.76, each p <0.001). CONCLUSIONS: Baseline prostate atrophy in men with a prostate biopsy negative for prostate cancer was independently associated with subsequent lower prostate cancer detection.

A multicenter phase I dose escalation trial to evaluate safety and tolerability of intra-arterial temozolomide for patients with advanced extremity melanoma using normothermic isolated limb infusion.

BACKGROUND: L-phenylalanine mustard (LPAM) has been the standard for use in regional chemotherapy (RC) for unresectable in-transit melanoma. Preclinical data demonstrated that regional temozolomide (TMZ) may be more effective. METHODS: Patients with AJCC Stage IIIB or IIIC extremity melanoma who failed previous LPAM-based RC were treated with TMZ via isolated limb infusion (ILI) according to a modified accelerated titration design. Drug pharmacokinetic (PK) analysis, tumor gene expression, methylation status of the O6-methylguanine methyltransferase (MGMT) promoter, and MGMT expression were evaluated. Primary objectives were to (1) determine dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of TMZ via ILI and (2) explore biomarker correlates of response. RESULTS: 28 patients completed treatment over 2.5 years at 3 institutions. 19 patients were treated at the MTD defined as 3,200 mg/m(2) [multiplied by 0.09 (arm), 0.18 (leg)]. Two of five patients had DLTs at the 3,600 mg/m(2) level while only grade 1 (n = 15) and grade 2 (n = 4) clinical toxicities occurred at the MTD. At 3-month post-ILI, 10.5 % (2/19) had CR, 5.3 % (1/19) had PR, 15.8 % (3/19) had SD, and 68.4 % (13/19) had PD. Neither PK parameters of TMZ nor MGMT levels were associated with response or toxicity. CONCLUSION: In this first ever use of intra-arterial TMZ in ILI for melanoma, the MTD was determined. While we could not define a marker for TMZ response, the minimal toxicity of TMZ ILI may allow for repeated treatments to increase the response rate as well as clarify the role of MGMT expression.

Predictors of pregnant quitters' intention to return to smoking postpartum.

INTRODUCTION: Although many pregnant women quit smoking, most return to smoking postpartum. Returning to smoking is strongly related to women's stated intention about smoking during pregnancy. We examined factors related to women's intention to return to smoking to improve intervention trials. METHODS: We report cross-sectional baseline data from a randomized controlled trial to prevent postpartum return to smoking. Women (n = 382; 98% consent rate) were English-speaking women who smoked at least 100 cigarettes in their lifetimes and at least 5 cigarettes a day prior to becoming pregnant. We fit logistic regression models to test whether women's intention to return to smoking was associated with demographic and smoking factors such as race, parity, and smoker self-identity. RESULTS: Forty-three percent of women had a strong intention of returning to smoking. Factors independently associated with intending to return to smoking were: stating they did not want to be currently pregnant (OR = 2.1, CI = 1.1-3.9), reporting being abstinent for fewer days (OR = 0.8, CI = 0.7-0.9), being less concerned about the harmful effects of smoking to themselves (OR = 1.6, CI = 0.9-2.8), viewing quit as temporary (OR = 2.1, CI = 1.2-3.6), and self-identifying selves as smokers (OR = 8.7, CI = 5.0-15.2). CONCLUSIONS: Although some factors related to intention to return to smoking were unchangeable, it might be possible to attempt to change women's attribution of why they quit to be more permanent and to have them change their self-identity to be a "nonsmoker" from a "smoker who is not currently smoking." Helping women have stronger intentions to stay quit could promote less return to smoking postpartum.

Cost-effectiveness of BRCA1 and BRCA2 mutation testing to target PARP inhibitor use in platinum-sensitive recurrent ovarian cancer.

OBJECTIVES: (1) To determine whether use of a PARP inhibitor or (2) BRCA1/2 mutation testing followed by a PARP inhibitor for test positives is potentially cost-effective for maintenance treatment of platinum-sensitive recurrent high-grade serous ovarian cancer. METHODS: A modified Markov decision analysis compared 3 strategies: (1) observe; (2) olaparib to progression; (3) BRCA1/2 mutation testing; treat mutation carriers with olaparib to progression. Progression-free survival and rates of adverse events were derived from a phase 2 randomized trial. Key assumptions are as follows: (1) 14% of patients harbor a BRCA1/2 mutation; (2) progression-free survival of individuals treated with olaparib is improved for BCRA1/2 carriers compared with noncarriers (estimated hazard ratio, approximately 0.4). Costs derived from national data were assigned to treatments, adverse events, and BRCA1/2 test. Monte Carlo probabilistic sensitivity analysis was performed. RESULTS: Global olaparib was the most effective strategy, followed by BRCA1/2 testing and no olaparib. BRCA1/2 testing had an incremental cost-effectiveness ratio (ICER) of $193,442 per progression-free year of life saved (PF-YLS) compared to no olaparib, whereas global olaparib had an ICER of $234,128 per PF-YLS compared to BRCA1/2 testing. At a 52% lower-than-baseline olaparib cost estimate of $3000 per month, BRCA1/2 testing became potentially cost-effective compared with observation, with an ICER of $100,000 per PF-YLS. When strategy (1) was removed from the analysis, BRCA1/2 testing was the preferred strategy. CONCLUSIONS: The use of maintenance olaparib in women with high-grade serous ovarian cancer is not cost-effective regardless of whether BRCA1/2 testing is used to direct treatment. However, BRCA1/2 testing is a preferred strategy compared to global maintenance olaparib alone.

Patterns of recurrence following complete response to regional chemotherapy for in-transit melanoma.

BACKGROUND: Even after complete response (CR) to regional chemotherapy for in-transit melanoma, many patients develop recurrence. Understanding the probability, location, and timing of recurrences can optimize management strategies for this patient population. METHODS: A prospective database identified patients who underwent 81 first-time hyperthermic isolated limb perfusions (HILPs) and 133 first-time isolated limb infusions (ILIs). Response was defined using the response evaluation criteria in solid tumors; recurrence was defined as development of new disease after in-field CR. RESULTS: HILP exhibited a significantly higher CR rate than ILI (44 vs. 28 %, p = .01). Among 36 HILP-CRs and 37 ILI-CRs, the 3-year recurrence rate was 65 % (95 % confidence interval [95 % CI]: 43-79 %) and 85 % (95 % CI: 63-94%), respectively. Median time to first recurrence was longer for HILP-CR than ILI-CR (23 vs. 8 months, p = .02). There was no statistically significant difference in median time to in-field recurrence between HILP-CR and ILI-CR (46 vs. 25 months, p = .15), but HILP-CR showed a longer median time to out-of-field recurrence (42 vs. 14 months, p = .02). Finally, the overall survival (OS) difference between HILP-CR and ILI-CR (3-year survival: 77 vs. 54 %) did not achieve statistical significance (p = .10). CONCLUSIONS: In the largest series comparing patterns of recurrence, we demonstrate that out-of-field recurrence after CR to HILP occurs later than after CR to ILI, though control of in-field disease remains similar. There remains no statistically significant difference in overall survival after CR to the 2 procedures.

Parent-focused change to prevent obesity in preschoolers: results from the KAN-DO study.

OBJECTIVE: The study presents the immediate post-intervention results of Kids and Adults Now - Defeat Obesity!, a randomized controlled trial to enhance healthy lifestyle behaviors in mother-preschooler (2-5 years old) dyads in North Carolina (2007-2011). The outcomes include change from baseline in the child's diet, physical activity and weight, and in the mother's parenting behaviors, diet, physical activity, and weight. METHOD: The intervention targeted parenting through maternal emotion regulation, home environment, feeding practices, and modeling of healthy behaviors. 400 mother-child dyads were randomized. RESULTS: Mothers in the intervention arm, compared to the control arm, reduced instrumental feeding (-0.24 vs. 0.01, p<0.001) and TV snacks (-.069 vs. -0.24, p=0.001). There were also improvements in emotional feeding (p=0.03), mother's sugary beverage (p=0.03) and fruit/vegetable (p=0.04) intake, and dinners eaten in front of TV (p=0.01); these differences were not significant after adjustment for multiple comparisons. CONCLUSION: KAN-DO, designed to maximize the capacity of mothers as agents of change, improved several channels of maternal influence. There were no group differences in the primary outcomes, but differences were observed in the parenting and maternal outcomes and there were trends toward improvement in the preschoolers' diets. Long-term follow-up will address whether these short-term trends ultimately improve weight status.

Feasibility of low-dose interleukin-2 therapy following T-cell-depleted nonmyeloablative allogeneic hematopoietic stem cell transplantation from HLA-matched or -mismatched family member donors.

INTRODUCTION: High relapse rates and infections remain primary causes of failure in nonmyeloablative transplantation. Interleukin-2 (IL-2) may stimulate the immune system and improve outcomes. The primary objective of this pilot study was to evaluate the feasibility of administering IL-2 following a T-cell-depleted nonmyeloablative hematopoietic stem cell transplant. METHODS: Patients received T-cell-depleted nonmyeloablative transplant from a matched or mismatched related donor. Those with allogeneic engraftment,

The lung cancer exercise training study: a randomized trial of aerobic training, resistance training, or both in postsurgical lung cancer patients: rationale and design.

BACKGROUND: The Lung Cancer Exercise Training Study (LUNGEVITY) is a randomized trial to investigate the efficacy of different types of exercise training on cardiorespiratory fitness (VO2peak), patient-reported outcomes, and the organ components that govern VO2peak in post-operative non-small cell lung cancer (NSCLC) patients. METHODS/DESIGN: Using a single-center, randomized design, 160 subjects (40 patients/study arm) with histologically confirmed stage I-IIIA NSCLC following curative-intent complete surgical resection at Duke University Medical Center (DUMC) will be potentially eligible for this trial. Following baseline assessments, eligible participants will be randomly assigned to one of four conditions: (1) aerobic training alone, (2) resistance training alone, (3) the combination of aerobic and resistance training, or (4) attention-control (progressive stretching). The ultimate goal for all exercise training groups will be 3 supervised exercise sessions per week an intensity above 70% of the individually determined VO2peak for aerobic training and an intensity between 60 and 80% of one-repetition maximum for resistance training, for 30-45 minutes/session. Progressive stretching will be matched to the exercise groups in terms of program length (i.e., 16 weeks), social interaction (participants will receive one-on-one instruction), and duration (30-45 mins/session). The primary study endpoint is VO2peak. Secondary endpoints include: patient-reported outcomes (PROs) (e.g., quality of life, fatigue, depression, etc.) and organ components of the oxygen cascade (i.e., pulmonary function, cardiac function, skeletal muscle function). All endpoints will be assessed at baseline and postintervention (16 weeks). Substudies will include genetic studies regarding individual responses to an exercise stimulus, theoretical determinants of exercise adherence, examination of the psychological mediators of the exercise - PRO relationship, and exercise-induced changes in gene expression. DISCUSSION: VO2peak is becoming increasingly recognized as an outcome of major importance in NSCLC. LUNGEVITY will identify the optimal form of exercise training for NSCLC survivors as well as provide insight into the physiological mechanisms underlying this effect. Overall, this study will contribute to the establishment of clinical exercise therapy rehabilitation guidelines for patients across the entire NSCLC continuum. TRIAL REGISTRATION: NCT00018255.

Effect of breast-feeding on weight retention at 3 and 6 months postpartum: data from the North Carolina WIC Programme.

OBJECTIVE: Pregnancy-related weight retention can contribute to obesity, and breast-feeding may facilitate postpartum weight loss. We investigated the effect of breast-feeding on postpartum weight retention. DESIGN: A retrospective follow-up study of weight retention, compared in women who were fully breast-feeding, combining breast-feeding with formula-feeding (mixed feeding), or formula-feeding at 3 months (n 14 330) or 6 months (n 4922) postpartum, controlling for demographic and weight-related covariates using multiple linear regression. SETTING: The North Carolina Special Supplemental Nutrition Program for Women, Infants, and Children (WIC). SUBJECTS: Participants in the North Carolina WIC Programme who delivered a baby between 1996 and 2004. RESULTS: In covariate-adjusted analyses, there was no association between breast-feeding and weight retention at 3 months postpartum. At 6 months postpartum, as compared to formula-feeders, mean weight retention was 0·84 kg lower in mixed feeders (95 % CI 0·39, 1·29; P = 0·0002) and 1·38 kg lower in full breast-feeders (95 % CI 0·89, 1·87; P ≤ 0·0001). CONCLUSIONS: Breast-feeding was inversely associated with weight retention at 6 months postpartum in this large, racially diverse sample of low-income women. Further, full breast-feeding had a larger protective effect than did breast-feeding combined with formula-feeding.

Predictors of adverse events among pregnant smokers exposed in a nicotine replacement therapy trial.

OBJECTIVE: The purpose of this study was to determine the contribution of randomization to nicotine replacement therapy (NRT), sociodemographic and psychosocial factors, and pregnancy and medical history to serious perinatal adverse events among pregnant smokers. STUDY DESIGN: We performed a retrospective review of all medical records for participants in the Baby Steps Trial. Data that were abstracted from 157 records were combined with baseline characteristics for logistic regression modeling of serious adverse events and adjusted for covariates. RESULTS: Serious adverse events occurred in 17% (9/52 pregnancies) and 31% (33/105 pregnancies) of participants in the control and NRT arms, respectively. Black race, adverse pregnancy history, and use of analgesic medication during pregnancy were significant predictors (P = .02, .04, and .01, respectively). Remaining covariates, which included randomization to NRT, were not statistically significant. CONCLUSION: Although race, poor pregnancy history, and use of analgesics were associated with serious adverse events, randomization to NRT during pregnancy was not a significant factor. Further research is needed to examine the safety of analgesic medications during pregnancy.

Reach out to ENhancE Wellness in Older Cancer Survivors (RENEW): design, methods and recruitment challenges of a home-based exercise and diet intervention to improve physical function among long-term survivors of breast, prostate, and colorectal cancer.

OBJECTIVE: Cure rates for cancer are increasing, especially for breast, prostate, and colorectal cancer. Despite positive trends in survivorship, a cancer diagnosis can trigger accelerated functional decline that can threaten independence, reduce quality-of-life and increase healthcare costs, especially among the elderly who comprise the majority of survivors. Lifestyle interventions may hold promise in reorienting functional decline in older cancer survivors, but few studies have been conducted. METHODS: We describe the design and methods of a randomized controlled trial, RENEW (Reach out to ENhancE Wellness), that tests whether a home-based multi-behavior intervention focused on exercise, and including a low saturated fat, plant-based diet, would improve physical functioning among 641 older, long-term (>or=5 years post-diagnosis) survivors of breast, prostate, or colorectal cancer. Challenges to recruitment are examined. RESULTS: Twenty thousand and fifteen cases were approached, and screened using a two-step screening process to assure eligibility. This population of long-term, elderly cancer survivors had lower rates of response (approximately 11%) and higher rates of ineligibility (approximately 70%) than our previous intervention studies conducted on adults with newly diagnosed cancer. Significantly higher response rates were noted among survivors who were White, younger, and more proximal to diagnosis and breast cancer survivors (p-values<0.001). CONCLUSION: Older cancer survivors represent a vulnerable population for whom lifestyle interventions may hold promise. RENEW may provide guidance in allocating limited resources in order to maximize recruitment efforts aimed at this needy, but hard-to-reach population.

Adherence to nicotine replacement therapy among pregnant smokers.

INTRODUCTION: This secondary analysis examined the association between adherence to nicotine replacement therapy (NRT) and smoking cessation among pregnant smokers enrolled in Baby Steps, an open-label randomized controlled trial testing cognitive-behavioral therapy (CBT) versus CBT plus NRT. METHOD: The analysis included only women who received NRT for whom we had complete data (N = 104). Data came from daily calendars created from recordings of counseling sessions and from telephone surveys at baseline and 38 weeks gestation. RESULTS: Overall, 29% of the 104 women used NRT for the recommended 6 weeks and 41% used NRT as directed in the first 48 hr after a quit attempt. Ordinal logistic regression modeling indicated that using NRT as directed in the first 48 hr and having made a previous quit attempt were the strongest predictors of longer NRT use. Univariate analyses suggested that primigravid women and women who used NRT longer were more likely to report quitting at 38 weeks gestation. DISCUSSION: Findings indicated that adherence to NRT is low among pregnant smokers, but adherence was a predictor of cessation. Future trials should emphasize adherence, particularly more days on NRT, to promote cessation during pregnancy.

Effects of home-based diet and exercise on functional outcomes among older, overweight long-term cancer survivors: RENEW: a randomized controlled trial.

CONTEXT: Five-year survival rates for early stage colorectal, breast, and prostate cancer currently exceed 90% and are increasing. Cancer survivors are at greater risk for second malignancies, other comorbidities, and accelerated functional decline. Lifestyle interventions may provide benefit, but it is unknown whether long-term cancer survivors can modify their lifestyle behaviors sufficiently to improve functional status. OBJECTIVE: To determine whether a telephone counseling and mailed print material-based diet and exercise intervention is effective in reorienting functional decline in older, overweight cancer survivors. DESIGN, SETTING, AND PARTICIPANTS: Randomized controlled trial of 641 overweight (body mass index > or = 25 and < 40), long-term (> or = 5 years) survivors (aged 65-91 years) of colorectal, breast, and prostate cancer, who were randomly assigned to an intervention group (n = 319) or delayed intervention (control) group (n = 322) in Canada, the United Kingdom, and 21 US states. Individuals were recruited for the Reach out to Enhance Wellness (RENEW) trial from July 1, 2005, through May 17, 2007. INTERVENTION: A 12-month, home-based tailored program of telephone counseling and mailed materials promoting exercise, improved diet quality, and modest weight loss. The control group was wait-listed for 12 months. MAIN OUTCOME MEASURES: Change in self-reported physical function on the Short-Form 36 physical function subscale (score range, 0-100; a high score indicates better functioning) from baseline to 12 months was the primary end point. Secondary outcomes included changes in function on the basic and advanced lower extremity function subscales of the Late Life Function and Disability Index (score range, 0-100), physical activity, body mass index, and overall health-related quality of life. RESULTS: The mean baseline Short-Form 36 physical function score was 75.7. At the 12-month follow-up, the mean function scores declined less rapidly in the intervention group (-2.15; 95% confidence interval [CI], -0.36 to -3.93) compared with the control group (-4.84; 95% CI, -3.04 to -6.63) (P = .03). The mean baseline basic lower extremity function score was 78.2. The mean changes in basic lower extremity function were 0.34 (95% CI, -0.84 to 1.52) in the intervention group compared with -1.89 (95% CI, -0.70 to -3.09) in the control group (P = .005). Physical activity, dietary behaviors, and overall quality of life increased significantly in the intervention group compared with the control group, and weight loss also was greater (2.06 kg [95% CI, 1.69 to 2.43 kg] vs 0.92 kg [95% CI, 0.51 to 1.33 kg], respectively; P < .001). CONCLUSION: Among older, long-term survivors of colorectal, breast, and prostate cancer, a diet and exercise intervention reduced the rate of self-reported functional decline compared with no intervention. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00303875.

Differences in baseline characteristics and outcomes at 1- and 2-year follow-up of cancer survivors accrued via self-referral versus cancer registry in the FRESH START Diet and exercise trial.

Participant accrual to research studies is a challenge; oftentimes, advertisements are used to supplement cases ascertained through clinic caseloads and cancer registries. It is unknown, however, if cases ascertained through these two sources differ. In this study, we compared self-referred (n = 209) and registry-ascertained (n = 334) participants enrolled in FRESH START, a randomized controlled trial promoting a healthy diet and increased exercise among breast and prostate cancer survivors. The two groups were compared on baseline characteristics, adherence, attrition, and outcomes by study arm. Compared with participants enrolled from registries, self-referrals were significantly younger (54.1 +/- 10.4 versus 58.7 +/- 10.7 years), more likely to have later-stage disease and to have received chemotherapy (40% versus 19%), and more likely to report "fighting spirit" coping styles (50% versus 30%), lower quality-of-life (88.2 +/- 15.1 versus 92.0 +/- 12.9), fewer comorbid conditions (1.87 +/- 1.60 versus 2.24 +/- 1.78), and lower consumption of five or more daily servings of fruits and vegetables (35% versus 45%; P values <0.05). Although no differences in behavior change were observed between self-referred and registry-ascertained cases assigned to the tailored intervention arm, this was not the case within the attention control arm. Among those who received the attention control intervention of standardized materials in the public domain, self-referred versus registry-ascertained participants showed significantly greater increases in exercise at 1-year follow-up and significantly greater increases in fruit and vegetable consumption at both 1- and 2-year follow-up (P values <0.05). Several differences exist between self-referred and registry-ascertained participants, including motivation to respond to standardized educational materials, which appears significantly greater in self-referred populations.

Evaluating the evidence: statistical methods in randomized controlled trials in the urological literature.

PURPOSE: Randomized controlled trials potentially provide the highest level of evidence to inform clinical decision making. Appropriate use of statistical methods is a critical aspect of all clinical research, including randomized controlled trials. We report the first formal evaluation to our knowledge of the statistical methods of randomized controlled trials published in the urological literature in 1996 and 2004. MATERIALS AND METHODS: All human subjects randomized controlled trials published in 4 leading urology journals in 1996 and 2004 were identified for formal review. A standardized evaluation form was developed based on the Consolidated Standards of Reporting Trials statement. Each article was evaluated by 2 independent reviewers with formal training in research design and biostatistics who were blinded to study authors and institution. Discrepancies were settled by consensus. RESULTS: A total of 152 randomized controlled trials were reviewed (65 in 1996, 87 in 2004). The median sample size (IQR) per arm of parallel design randomized controlled trials published in 1996 and 2004 was 36 (11, 96) and 50 (26, 134) study subjects, respectively (p = 0.157). Sample size justifications were provided by 19% of studies in 1996 and 47% of studies in 2004 (p = 0.001). Of randomized controlled trials 16 (25%) vs 32 (37%) identified a single primary outcome variable (p = 0.110). Effect size estimates for primary or secondary outcome variables were provided by 5% vs 13% (p = 0.090) and the precision of the effect was detailed by 5% vs 10% of randomized controlled trials (p = 0.195). CONCLUSIONS: This formal review suggests that statistical analysis in urological randomized controlled trials has improved. However, considerable deficiencies remain. Ongoing education in applied statistics may further improve urological randomized controlled trial reporting.